Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome

New Fertility Drug for Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is one of the most common sources of decreased fertility, sometimes called subfertility, affecting between 5-10% of women of childbearing age.1 Women with PCOS produce more male hormones (androgens) than normal, which can cause weight gain, acne, and increased hair growth. This hormonal imbalance impairs the maturation and release of the woman’s eggs. When eggs aren’t released via ovulation, there is low production of progesterone (the female hormone that builds up the uterine lining), leading to an irregular menstrual cycle.2 Furthermore, those unreleased eggs may become ovarian cysts, which can cause pelvic pain and ovulation problems, and further threaten the health of the ovaries.3

For women with PCOS who don’t want to get pregnant right now, taking birth control pills can reduce the androgen imbalance by replenishing lacking female hormones, thus promoting regular menses. To get pregnant, however, women with PCOS often need medication to stimulate ovulation, and may even resort to expensive in vitro fertilization (IVF).4 Weight loss is also a powerful tool to reduce insulin resistance and androgen overproduction, but these very hormonal imbalances make attaining a healthy weight especially difficult for women with PCOS.

The first-choice treatment to stimulate ovulation has long been Clomiphene, a drug that disinhibits the release of the pituitary hormones that promote ovulation (follicle-stimulating and luteinizing hormone).5 However, this drug only leads to a live birth for about 22% of women even after five months of trying, and has a high rate of multiple-gestation pregnancies.4 One potential alternative to Clomiphene is Letrozole, a drug that induces ovary-stimulating hormone release by reducing estrogen production .6 Some studies have suggested Letrozole, a drug commonly used for breast cancer treatment, may not only be effective in inducing ovulation in women with PCOS, but may lead to fewer multiple births than does Clomiphene.7

To rigorously test whether Letrozole is as effective as Clomiphene and to study its safety profile, a multicenter double-blind trial randomly designated 750 women with PCOS to take either Letrozole or Clomiphene to treat their infertility for a period of five months.8 As is typical for women with PCOS, both groups showed baseline metabolic dysfunction, obesity, and elevated androgen levels.9 Overall, women who took Letrozole had more live births (27.5%) than did women who took Clomiphene (19.1%).10 Those taking Letrozole experienced a higher rate of ovulation by their second visit, and were more likely to have single-gestation pregnancies. There were no significant differences in pregnancy loss after conception. While rates of fetal developmental anomalies were similar between the two treatment groups, further research is necessary to establish the safety of prenatal exposure to Letrozole. Finally, women whose body mass index (BMI) was less than 30 had the highest likelihood of conceiving, while women with a BMI over 39.4 had the lowest. 10

What this means for you:
Because of this study, the preferred fertility medications for women with PCOS may soon be changing. Since these findings are very recent and more studies still need to be performed, your doctor may wait until more data is available before incorporating Letrozole into PCOS fertility treatment. However, if you’re a woman with PCOS who might be looking to conceive a few years from now, the findings of this study may well influence which fertility treatment your doctor chooses to prescribe in the future.